Network of microbial and antibiotic interactions drive colonization and infection with multidrug-resistant organisms

Abstract

The emergence and spread of multidrug-resistant organisms (MDROs) across global healthcare networks poses a serious threat to hospitalized individuals. Strategies to limit the emergence and spread of MDROs include oversight to decrease selective pressure for MDROs by promoting appropriate antibiotic use via antibiotic stewardship programs. However, restricting the use of one antibiotic often requires a compensatory increase in the use of other antibiotics, which in turn selects for the emergence of different MDRO species. Further, the downstream effects of antibiotic treatment decisions may also be influenced by functional interactions among different MDRO species, with the potential clinical implications of such interactions remaining largely unexplored. Here, we attempt to decipher the influence network between antibiotic treatment, MDRO colonization, and infection by leveraging active surveillance and antibiotic treatment data for 234 nursing home residents. Our analysis revealed a complex network of interactions: antibiotic use was a risk factor for primary MDRO colonization, which in turn increased the likelihood of colonization and infection by other MDROs. When we focused on the risk of catheterassociated urinary tract infections (CAUTI) caused by Escherichia coli, Enterococcus, and Staphylococcus aureus we observed that cocolonization with specific pairs of MDROs increased the risk of CAUTI, signifying the involvement of microbial interactions in CAUTI pathogenesis. In summary, our work demonstrates the existence of an underappreciated healthcare-associated ecosystem and strongly suggests that effective control of overall MDRO burden will require stewardship interventions that take into account both primary and secondary impacts of antibiotic treatments.multidrug-resistant organisms | nursing homes | long-term care facilities | antibiotics | catheter-associated urinary tract infection T he successful treatment of bacterial infections has been significantly undermined by the emergence and spread of multidrug-resistant organisms (MDROs) (1). Antibiotic-resistant healthcare-acquired infections are of particular concern, as MDROs complicate treatment of infections, hinder effective treatment of comorbid conditions, and increase risk of morbidity and mortality (2-5). While the threats of MDROs in acute-care hospitals are well known, MDROs are not limited to those settings. In particular, residents in long-term care facilities (LTCFs) often have underlying medical conditions that make them particularly vulnerable to infections. Moreover, the high rates of MDRO colonization (6) and antibiotic use (7-9) among LTCF residents further put this population at risk for contracting infections. Furthermore, the frequent transfers between LTCFs and other healthcare facilities leads to the dissemination of MDROs throughout the healthcare network, creating a substantial economic and clinical burden that permeates healthcare systems (10, 11).Given the central role of antibiotic use in both the emergence and proliferation of...

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

“…Additionally, those who are colonized can transmit MDROs to patients vulnerable to infection in the hospital setting. Antibiotics kill subsets of commensal gut bacteria and allow for the unchecked growth of pathogenic species, causing antibiotic use to be a major risk factor for MDRO colonization and infection [7].…”

A rare opportunist,Morganella morganii, decreases severity of polymicrobial catheter-associated urinary tract infection

“…Furthermore, there are increasing reports of isolates producing extended-spectrum β-lactamases (ESBL) and carbapenemases (25–29), which threatens the utility of last-resort antibiotics and increases the mortality rate for P. mirabilis infection (30–32). P. mirabilis also acts as a “hub” species in catheterized nursing home residents, promoting colonization by additional multidrug resistance organisms (33) and providing protection from antibiotic treatment (34). Furthermore, P. mirabilis produces a potent urease enzyme that hydrolyzes the urea in urine to carbon dioxide and ammonia, thereby increasing urine pH and facilitating the precipitation of polyvalent ions and resulting in struvite crystals, catheter encrustation, blockage, and formation of urinary stones (urolithiasis) (35–37).…”

Evaluating Efficacy of Antimicrobial and Antifouling Materials for Urinary Tract Medical Devices: Challenges and Recommendations

“…Importantly, some uropathogen species are only able to colonize the catheter surface in the presence of others species . In line with this, it was recently suggested that interspecies interactions between multidrug‐resistant organisms should be considered when treating CAUTI by antibiotic therapy, as applications of antibiotics would select for specific resistant organisms that would then positively select for other multidrug‐resistant organisms through complex network interactions . Interactions resulting in enhanced virulence and antibiotic tolerance are not restricted to the bacterial kingdom; examples of bacteria–fungi interactions have also been described, mainly focusing on the interactions between S. aureus and C. albicans , where extended S. aureus invasion has been reported due to bacterial association to fungal hyphae .…”